Piezotronic effect determined neuron-like differentiation of adult stem cells driven by ultrasound

Electrical stimulation is an efficient approach to inducing neural differentiation of stem cells. However, most demonstrations of conventional electrical stimulation for the regulation of stem cell differentiation generally involve three components—an electrical signal generator, conductive culture substrate, and pair of lines, which limits its use in clinical applications for neural degeneration treatments. Herein, we proposed a facile method to generate localized electrical signals on the surface of a piezoelectric poly (vinylidene fluoride) (PVDF) film with a well-designed nanopillar array driven by ultrasound irradiation based on a piezotronic effect, which proved to induce neuronal differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) without any biological or chemical neural inducing factors. The assessment of rBMSCs on the surface of the PVDF nanopillar array at the gene and protein levels confirmed that rBMSCs could differentiate into neuron-like cells. This demonstration provides a practical approach for the regulation of adult stem cells to differentiate into neurons, which will be a great achievement to overcome the shortage of neural stem cells in the adult human body and realize the autologous stem cell treatment of neurodegeneration. This work creates a new therapeutic avenue for contactless, controlled neuroregenerative therapies.